Assessment of the cardiostimulant action of propionyl-L-carnitine on chronically volume-overloaded rat hearts

Abstract

Chronic volume overload was induced in young rats of Wistar strain by surgical opening of the aorto-caval fistula. Three months later, during in vitro perfusion with exogenous palmitate, left ventricular function and energy turnover (QO2) of hypertrophied hearts were severely depressed. This seemed to be related to impaired long-chain fatty acid utilization, as reflected by decreased 14CO2 production from U-14C-palmitate and decreased tissue levels of L-carnitine. Another group of rats exposed to chronic volume overload was pretreated for 2 weeks before sacrifice with propionyl-L-carnitine (250 mg/kg/day), and the hearts were perfused with 1.2 mM palmitate and 10 mM propionyl-L-carnitine. In this group, both mechanical performance and the oxygen consumption rate were quite comparable to those of untreated controls. On the other hand, tissue levels of L-carnitine were only slightly increased, and the rate of 14CO2 production from U-14C-palmitate was insignificantly improved. This suggests that propionyl-L-carnitine administration promotes the mechanical performance of normoxic volume-overloaded hearts via a mechanism other than improved palmitate utilization. The possibility that propionyl moieties themselves replenish with mitochondrial intermediates of the tricarboxylic cycle (malate, acetyl-CoA) is not excluded.